The loss of bladder control is called urinary incontinence. It occurs when the bladder muscles contract or the muscles surrounding the urethra relax without warning. Although urinary incontinence is observed in people of all ages, this disorder is more prevalent in older people. The U.S. National Institute on the Aging estimates that at least 1 in 10 people aged 65 or older suffer form urinary incontinence. Likewise, incontinence is a common condition in Australia and throughout the world, affecting from 12% of 18 year old women and up to 50% of women in their 70's. Symptoms can range from mild leaking to uncontrollable wetting. Women are more likely than men to have incontinence.
While aging, per se, does not cause urinary incontinence, it can occur for many reasons. For example, urinary tract infections, vaginal infection or irritation, constipation, and certain medicines can cause bladder control problems that may last only a short time. Sometimes incontinence lasts longer. Chronic incontinence can be caused by, e.g., weak bladder muscles, overactive bladder muscles, blockage from an enlarged prostate, damage to nerves that control the bladder from diseases such as multiple sclerosis or Parkinson's disease, or diseases such as arthritis that can make walking painful and slow.
There are multiple types of urinary incontinence which include, e.g., stress incontinence, urge incontinence, overflow incontinence and functional incontinence. Stress incontinence happens when urine leaks during exercise, coughing, sneezing, laughing, lifting heavy objects, or other body movements that put pressure on the bladder. It is the most common type of bladder control problem in younger and middle-age women. In some cases, it is related to childbirth. It may also begin around the time of menopause. Urge incontinence happens when people can't hold their urine long enough to get to the toilet in time. Healthy people can have urge incontinence, but it is often found in people who have diabetes, stroke, Alzheimer's disease, Parkinson's disease, or multiple sclerosis. It is also sometimes an early sign of bladder cancer. Overflow incontinence happens when small amounts of urine leak from a bladder that is always full. A man can have trouble emptying his bladder if an enlarged prostate is blocking the urethra. Diabetes and spinal cord injury can also cause this type of incontinence. Functional incontinence happens in many older people who have normal bladder control. They just have a hard time getting to the toilet in time because of arthritis or other disorders that make moving quickly difficult.
The current medical treatment options for urinary incontinence include behavioral interventions, e.g., bladder control training, drug medications, devices, e.g., catheters, and surgical procedures. Current drug therapy includes anticholinergics (with antispasmodic effects, e.g., oxybutinin), smooth muscle relaxants (antispasmodics), tricyclic antidepressants (e.g., imipramine), alpha-adrenergic antagonists, alpha-adrenergic agonists (e.g., phenylpropanolamine), prostaglandin synthesis inhibitors, calcium channel blockers and others (Sullivan and Abrams, Eur. Urol., 36 Suppl 1:89-95 (1999); Andersson, Baillieres Best Pract. Res. Clin. Obstet. Gynaecol., 14(2):291-313 (2000); Owens and Karram, Drug Saf., 19(2):123-39 (1998); Wada et al., Arch. Int. Pharmacodyn Ther., 330(1):76-89 (1995)). Unfortunately, most drug treatments are associated with unpleasant side effects, and this impacts on patient compliance (Sullivan and Abrams, Eur. Urol., 36 Suppl 1:89-95 (1999); Andersson, Baillieres Best Pract. Res. Clin. Obstet. Gynaecol., 14(2):291-313 (2000); Owens and Karram, Drug Saf., 19(2):123-39 (1998); Wada et al., Arch. Int. Pharmacodyn Ther., 330(1):76-89 (1995))2-5.
Acetylcholine is the primary excitatory neurotransmitter involved in bladder emptying. Certain drugs commonly prescribed for urinary incontinence, such as oxybutynin hydrochloride, inhibit the muscarinic action of acetylcholine on smooth muscle, producing a direct antispasmodic action. These drugs relax the detrusor muscle. Wada Y. et al., Arch. Int. Pharmacodyn. Ther., 330(1):76-89 (1995); Tapp A. J. S. et al., Brit. J. Obstetrics Gynecology, 97: 521-6 (1990). These medications also produce unwanted anticholinergic effects, such as dry mouth, blurred vision and constipation. Pathak A S, Aboseif S R. Overactive Bladder: Drug therapy versus nerve stimulation. Nat Clin Pract Urol, 2(7):310-311, 2005; Wein (2001). Natural therapies have also been investigated for this condition (Steels et al., Aust. Continence J., 7(2):34-37 (2001); Karantanis et al., Aust. Continence J., 6(4):6-7 (2000); Arya et al., Obstetrics and Gynecology, 96(1):85-89 (2000); Bryant et al., Aust. Continence J., 6(4):8 (2000)). In Ayurveda, Crateva nurvala is a drug highly regarded for its use in the management of uropathies (Nadkarni, Indian Materia Medica. Bombay Popular Prakashan). Western traditional treatments recommend the use of Equisetum arvense (British Herbal Pharmacopeia. Publ: British Herbal Medicine Association 1983). Isolated clinical studies conducted using herb-based natural therapies for urinary incontinence include Crateva nurvala herb, acupuncture and dietary intervention such as modification of dietary intake. Deshpande et al., Indian J. Med. Res. 76(supp): 46-53, 1982; Karantanis et al., Aust. Continence J., 6(4): 6-7, 2000; Arya et al., Obstetrics and Gynecology, 96(1): 87-89, 2000; Bryant et al., Aust. Continence J., 6(4): 8, 2000.
Overactive bladder (OAB) is a condition characterized by the sudden need to urinate. If that need results in the unintentional leakage of urine, the condition is called urge incontinence (“OAB wet”). Thus, urge incontinence falls within the general definition of OAB. OAB result from the sudden, involuntary contraction of the muscle in the wall of the urinary bladder. Approximately one-third of people with OAB also experience urge incontinence (“OAB wet”), while approximately two-thirds have OAB without urge incontinence (“OAB dry”). According to the National Overactive Bladder Evaluation, OAB affects 16.5% of the population, with 16.9% of women and 16.0% of men affected. Stewart et al., World J. Urol. 20: 327-336, (2003).
OAB, like urinary incontinence, is treated primarily with anticholinergic drugs (e.g., oxybutinin). These inhibit the neurotransmitter acetylcholine from attaching to the bladder muscle, and thereby reduce the frequency and intensity of contractions of the bladder. Unfortunately, adverse side effects of these drugs include dry mouth, dry eyes, constipation, and headache. Anderson, Urology, 3A: 32-41 (2004); Cruz, Urology. 3A: 65-73 (2004); Appell et al., Mayo Clinical Proc., 78:696-702. (2003).
There are currently no medications that specifically target incontinence symptoms without having side effects elsewhere in the body. There is a need for the identification of new herb-containing compositions for the prevention or treatment of urinary incontinence and overactive bladder.